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Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells.
Open accessAbstract
Human CD4+ T cells, activated by allogeneic monocytes in a primary mixed lymphocyte reaction in the presence of exogenous interleukin (IL) 10, specifically failed to proliferate after restimulation with the same alloantigens. A comparable state of T cell unresponsiveness could be induced by activation of CD4+ T cells by cross-linked anti-CD3 monoclonal antibodies (mAbs) in the presence of exogenous IL-10. The anergic T cells failed to produce IL-2, IL-5, IL-10, interferon gamma, tumor necrosis factor alpha, and granulocyte/macrophage colony-stimulating factor. The IL-10-induced anergic state was long-lasting. T cell anergy could not be reversed after restimulation of the cells with anti-CD3 and anti-CD28 mAbs, although CD3 and CD28 expression was normal. In addition, restimulation of anergized T cells with anti-CD3 mAbs induced normal Ca2+ fluxes and resulted in increased CD3, CD28, and class II major histocompatibility complex expression, indicating that calcineurin-mediated signaling occurs in these anergic cells. However, the expression of the IL-2 receptor alpha chain was not upregulated, which may account for the failure of exogenous IL-2 to reverse the anergic state. Interestingly, anergic T cells and their nonanergic counterparts showed comparable levels of proliferation and cytokine production after activation with phorbol myristate acetate and Ca2+ ionophore, indicating that a direct activation of a protein kinase C-dependent pathway can overcome the tolerizing effect of IL-10. Taken together, these data demonstrate that IL-10 induces T cell anergy and therefore may play an important role in the induction and maintenance of antigen-specific T cell tolerance.
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Metadata
- Authors
- Groux, H., Bigler, M., de Vries, J. E., & Roncarolo, M. G.
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1996-07-01
- Volume
- 184
- Issue
- 1
- Pages
- 19-29
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2139104516
- Cited by
- 777
- References
- 0
- FWCI
- 15.52
- Type
- journal article
- Language
- en
- Open access
- bronze
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